Controlling tumor progression and recurrence in mice through combined treatment with a PD-L1 inhibitor and a designer Salmonella strain that delivers GM-CSF.
10.1016/j.apsb.2024.07.011
- Author:
Heung Jin JEON
1
;
Daejin LIM
2
;
EunA SO
3
;
Solbi KIM
4
;
Jae-Ho JEONG
3
;
Miryoung SONG
5
;
Hyo-Jin LEE
1
Author Information
1. Infection Control Convergence Research Center, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea.
2. Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
3. Department of Microbiology, Chonnam National University Medical School, Gwangju 58128, Republic of Korea.
4. Department of Medical Science, Chungnam National University College of Medicine, Daejeon 35015, Republic of Korea.
5. Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin 17035, Republic of Korea.
- Publication Type:Journal Article
- Keywords:
Checkpoint inhibitor;
Granulocyte macrophage colony stimulating factor;
Programmed death-ligand 1;
Salmonella
- From:
Acta Pharmaceutica Sinica B
2024;14(12):5479-5492
- CountryChina
- Language:English
-
Abstract:
Combination therapy with checkpoint inhibitors blocks inhibitory immune cell signaling and improves clinical responses to anticancer treatments. However, continued development of innovative and controllable delivery systems for immune-stimulating agents is necessary to optimize clinical responses. Herein, we engineered Salmonella to deliver recombinant granulocyte macrophage colony stimulating factor (GM-CSF) in a controllable manner for combination treatment with a programmed death-ligand 1 (PD-L1) inhibitor. The engineered Salmonella enabled delivery of recombinant GM-CSF into mouse tumors, activating recruitment of immune cells, such as M1-polarized macrophages, dendritic cells, and CD8+ T cells. Combination treatment with the PD-L1 inhibitor and engineered Salmonella increased the survival rate of tumor-bearing mice by 25%. New tumor growth was strongly suppressed, and visible tumors disappeared at 120 days post-infection (dpi) in mice rechallenged with additional tumor implantation at 100 dpi. The number of memory T cells increased >2-fold in tumor-rechallenged mice. Our findings demonstrate superiority of the engineered Salmonella as a cancer therapeutic agent with precise targeting ability, immune-boosting activity, and ease of combination with other therapeutics.
